Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients.

Détails

ID Serval
serval:BIB_08E3B822BB7E
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Etude de cas (case report): rapporte une observation et la commente brièvement.
Collection
Publications
Institution
Titre
Increased clozapine plasma concentrations and side effects induced by smoking cessation in 2 CYP1A2 genotyped patients.
Périodique
Therapeutic drug monitoring
Auteur(s)
Bondolfi G., Morel F., Crettol S., Rachid F., Baumann P., Eap C.B.
ISSN
0163-4356
Statut éditorial
Publié
Date de publication
2005
Peer-reviewed
Oui
Volume
27
Numéro
4
Pages
539-43
Langue
anglais
Notes
Publication types: Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't - Publication Status: ppublish
Résumé
Clozapine, an atypical antipsychotic, depends mainly on cytochrome P4501A2 (CYP1A2) for its metabolic clearance. CYP1A2 is inducible by smoking, and lower plasma concentrations of clozapine are measured in smokers than in nonsmokers. Case reports have been published on the effects of discontinuing smoking in patients receiving clozapine, which might lead to elevated plasma concentrations and severe side effects. We present 2 cases on the consequences of smoking cessation in patients receiving this drug. In the first patient, smoking cessation resulted, within 2 weeks, in severe sedation and fatigue, with an approximately 3-fold increase of plasma clozapine concentrations. In the second patient, a very high plasma concentration of clozapine (3004 ng/mL) was measured 6 days following a 16-day stay in a general hospital, during which smoking was prohibited. In the latter patient, the replacement of omeprazole, a strong CYP1A2 inducer, by pantoprazole, a weaker CYP1A2 inducer, could have contributed, in addition to smoking cessation, to the observed strong increase of plasma clozapine concentrations. Genotyping of the 2 patients revealed that they were carriers of the AA genotype for the -164C>A polymorphism (CYP1A2*1F) in intron 1 of CYP1A2 gene, which has previously been shown to confer a high inducibility of CYP1A2 by smoking. Thus, at the initiation of clozapine treatment, smoking patients should be informed that, if they decide to stop smoking, they are encouraged to do so but must inform their prescriber beforehand. Also, because of the increased use of no-smoking policies in many hospitals, studies examining the consequences of such policies on the pharmacokinetics/pharmacodynamics of drugs metabolized by CYP1A2, taking into account different CYP1A2 genotypes, are needed.
Mots-clé
Adult, Antipsychotic Agents, Clozapine, Cytochrome P-450 CYP1A2, Fatigue, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Psychotic Disorders, Schizophrenia, Paranoid, Smoking Cessation, Treatment Outcome
Pubmed
Web of science
Création de la notice
10/03/2008 11:54
Dernière modification de la notice
20/08/2019 13:31
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